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Abstract:

Haemophilus influenzae is the most important pathogen of Haemophilus genus in humans. Resistance to β-lactams has been documented in this species, however, most β-lactam antibiotics are still widely used for treatment of H.influenzae infections. In order to minimise treatment failure, the anti-microbial efficiency of drugs should be monitored regularly. In this study the prevalence of β-lacam resistance in clinical strains of H.influenzae was determined in Scotland. Six hundred and sixteen isolates were collected from four hospitals during 1993-1995. 20.5% of the strains contained a β-lactamase enzyme. There are marked regional differences in the proportion of β-lactamase producing isolates which ranges from 9.6% in Glasgow Royal Infirmary to 33.3% in Edinburgh Royal Infirmary. The concentrations required for ampicillin, amoxycillin/clavulanic acid, cefuroximine, ceftazidime, cefotaxime, cefaclor and imipenem to inhibit 50% and 90% of the isolates were determined and compared to the surveys in other countries. H.influenzae biotypes I, II and III are the most prevalent biogroups in Scotland especially among the over 50 year old adults. β-lactam resistance was observed in all biogroups of H.influenzae. Among the clinical isolates, one strain from Glasgow Southern General Hospital, although remained sensitive to ampicillin, was found to be β-lactamase positive. A cell free extract of this strain was examined by isoelectric focusing and β-lactamase activity was visualised at a pI of 7.9. This novel enzyme, VAT-1, did not cofocus with any of the controls or any of their extended spectrum derivatives, nor was it indicative of plasmid encoded β-lactamases associated with other respiratory pathogens. Biochemical analysis indicated that VAT-1 had a substrate profile of a cephalosporinase that hydrolysed first generation cephalosporins. Inhibitor analysis demonstrated that VAT-1 was a class C β-lactamase and it is only the third β-lactamase that has been described in H.influenzae.